Protein translation by the ribosome is essential for cellular life but not much is known about the molecular mechanisms governing how ribosomes are made. Ribosome biogenesis is a major consumer of cellular energy and an incredibly complex pathway involving more than 300 trans-acting factors that is regulated by well-known tumor suppressors including p53 and Rb as well as protoncogenes such as cMyc and TOR, and is emerging in the field as a new target for cancer therapy. Currently we are taking a structure/function approach to decipher the roles of several protein complexes that are essential for ribosome assembly and cell viability. Through a combination of x-ray crystallography, yeast genetics, and immunofluorescence we have been able to reveal how a well conserved pre-rRNA processing complex is released from pre-ribosome particles in the nucleolus in both yeast and mammalian cells.